Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma.
Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma.
复制标题
靶向表皮生长因子受体变体 III 的适体缀合聚乙二醇化量子点用于神经胶质瘤荧光成像
DOI：
10.2147/ijn.s133166
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发表时间：
2017
影响因子：
8
通讯作者：
Cheng Y
中科院分区：
文献类型：
--
作者：
Tang J;Huang N;Zhang X;Zhou T;Tan Y;Pi J;Pi L;Cheng S;Zheng H;Cheng Y
切除范围是神经胶质瘤患者的重要预后因素。然而，由于肿瘤固有的浸润特性，最大安全切除水平很难确定。最近，荧光引导手术已成为一种可以安全切除神经胶质瘤的新技术。在本研究中，我们通过将适配体32（A32）缀合到量子点（QD）表面构建了一种新型量子点（QD）标记适配体（QD-Apt）纳米探针，它可以与肿瘤特异性结合。 A32是一种单链DNA，能够与特异分布在胶质瘤细胞表面的表皮生长因子受体变体III（EGFRvIII）结合。为检测人脑组织中EGFRvIII的表达情况，对120份标本（包括110份胶质瘤组织和10份正常脑组织）进行免疫组化检测，结果显示，胶质瘤组织中EGFRvIII的阳性表达率为41.82%，正常脑组织中的阳性表达率为0.00%。此外，QD-Apt 纳米颗粒（NP）的理化性质也得到了彻底的表征。对NPs的生物相容性进行了评估，结果表明QD-Apt在体内和体外均无毒。此外，还研究了 QD-Apt 在标记神经胶质瘤细胞系和人脑神经胶质瘤组织以及原位靶神经胶质瘤中的用途。我们发现QD-Apt不仅可以与U87-EGFRvIII胶质瘤细胞特异性结合，而且可以在体外与人胶质瘤组织结合。对携带 U87-EGFRvIII 的原位胶质瘤模型小鼠进行体内荧光成像表明，QD-Apt 可以穿透血脑屏障，然后通过与 EGFRvIII 结合选择性地在肿瘤中积累，从而产生强烈的荧光，从而使胶质瘤的边缘清晰可见，从而帮助外科医生实现胶质瘤的最大安全切除。此外，QD-Apt还可应用于胶质瘤的术前诊断和术后检查。因此，这些成果促进了肿瘤靶向荧光成像在胶质瘤的诊断、手术切除和术后检查中的应用。
The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs) were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling glioma cell lines and human brain glioma tissues, and target gliomas in situ was also investigated. We found that not only could QD-Apt specially bind to the U87-EGFRvIII glioma cells but also bind to human glioma tissues in vitro. Fluorescence imaging in vivo with orthotopic glioma model mice bearing U87-EGFRvIII showed that QD-Apt could penetrate the blood–brain barrier and then selectively accumulate in the tumors through binding to EGFRvIII, and consequently, generate a strong fluorescence, which contributed to the margins of gliomas that were visualized clearly, and thus, help the surgeons realize the maximum safe resection of glioma. In addition, QD-Apt can also be applied in preoperative diagnosis and postoperative examination of glioma. Therefore, these achievements facilitate the use of tumor-targeted fluorescence imaging in the diagnosis, surgical resection, and postoperative examination of glioma.